How the Environmental influences on Child Health Outcome (ECHO) Cohort can spur discoveries in environmental epidemiology.

NIH's Environmental influences on Child Health Outcome (ECHO) program is an innovative, large, collaborative research initiative whose mission is to enhance the health of children for generations to come. The goal of the ECHO Cohort is to examine effects of a broad array of early environmental exposures on child health and development. It includes longitudinal data and biospecimens from over 100,000 children and family members from diverse settings across the U.S. ECHO investigators have published collaborative analyses showing associations of environmental exposures--primarily in the developmentally sensitive pre-, peri-, and post-natal periods--with preterm birth and childhood asthma, obesity, neurodevelopment, and positive health. Investigators have addressed health disparities, joint effects of environmental and social determinants, and effects of mixtures of chemicals. The ECHO Cohort is now entering its second 7-year cycle (2023-2030), which will add the preconception period to its current focus on prenatal through adolescence. Through a controlled access public use database, ECHO makes its deidentified data available to the general scientific community. ECHO Cohort data provide opportunities to fill major knowledge gaps in in environmental epidemiology, and to inform policies, practices, and programs to enhance child health.

Principles and Practices of Returning Individual Research Results to Participants in Large Studies of Pregnancy and Childhood.

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of 'vulnerable' participants, including pregnant and pediatric participants. We present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desire to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers' availability to answer questions, and to provide as much information as possible about actionable steps to control environmental exposures associated with disease risk.

Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study.

OBJECTIVE: To determine if daily respiratory status improved more in extremely low gestational age (GA) premature infants after diuretic exposure compared with those not exposed in modern neonatal intensive care units. STUDY DESIGN: The Prematurity and Respiratory Outcomes Program (PROP) was a multicenter observational cohort study of 835 extremely premature infants, GAs of 230/7-286/7 weeks, enrolled in the first week of life from 13 US tertiary neonatal intensive care units. We analyzed the PROP study daily medication and respiratory support records of infants ≤34 weeks postmenstrual age. We determined whether there was a temporal association between the administration of diuretics and an acute change in respiratory status in premature infants in the neonatal intensive care unit, using an ordered categorical ranking of respiratory status. RESULTS: Infants in the diuretic exposed group of PROP were of lower mean GA and lower mean birth weight (P < .0001). Compared with infants unexposed to diuretics, the probability (adjusted for infant characteristics including GA, birth weight, sex, and respiratory status before receiving diuretics) that the exposed infants were on a higher level of respiratory support was significantly greater (OR, >1) for each day after the initial day of diuretic exposure. CONCLUSIONS: Our analysis did not support the ability of diuretics to substantially improve the extremely premature infant's respiratory status. Further study of both safety and efficacy of diuretics in this setting are warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01435187.

Adults born preterm: a review of general health and system-specific outcomes.

In this review of 126 publications, we report that an overwhelming majority of adults born at preterm gestations remain healthy and well. However, a small, but a significant fraction of them remain at higher risk for neurological, personality and behavioural abnormalities, cardio-pulmonary functional limitations, systemic hypertension and metabolic syndrome compared to their term-born counterparts. The magnitude of increased risk differed across organ systems and varied across reports. The risks were proportional to the degree of prematurity at birth and seemed to occur more frequently among preterm infants born in the final two decades of the 20th century and later. These findings have considerable public health and clinical practice relevance. CONCLUSION: Preterm birth needs to be considered a chronic condition, with a slight increase in the risk for long-term morbidities among adults born preterm. Therefore, obtaining a history of gestational age and weight at birth should be a routine part of care for patients of all age groups.

Cell therapy for lung diseases. Report from an NIH-NHLBI workshop, November 13-14, 2012.

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13-14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy.

Improving outcomes for pulmonary vascular disease.

Recognizing the importance of improving lung health through lung disease research, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of multidisciplinary experts for the following purpose: (1) to review the current scientific knowledge underlying the basis for treatment of adults and children with pulmonary vascular diseases (PVDs); (2) to identify gaps, barriers, and emerging scientific opportunities in translational PVD research and the means to capitalize on these opportunities; (3) to prioritize new research directions that would be expected to affect the clinical course of PVDs; and (4) to make recommendations to the NHLBI on how to fill identified gaps in adult and pediatric PVD clinical research. Workshop participants reviewed experiences from previous PVD clinical trials and ongoing clinical research networks with other lung disorders, including acute respiratory distress syndrome, chronic obstructive lung disease, and idiopathic pulmonary fibrosis, as well. Bioinformatics experts discussed strategies for applying cutting-edge health information technology to clinical studies. Participants in the workshop considered approaches in the following broad concept areas: (1) improved phenotyping to identify potential subjects for appropriate PVD clinical studies; (2) identification of potential new end points for assessing key outcomes and developing better-designed PVD clinical trials; and (3) the establishment of priorities for specific clinical research needed to advance care of patients with various subsets of PVDs from childhood through adulthood. This report provides a summary of the objectives and recommendations to the NHLBI concentrating on clinical research efforts that are needed to better diagnose and treat PVDs.

Asthma outcomes: exacerbations.

BACKGROUND: The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity. OBJECTIVE: National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies. METHODS: We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop in March 2010 and finalized in September 2011. RESULTS: No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting ß-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications. CONCLUSIONS: The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component.

National Heart, Lung, and Blood Institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities.

Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

Respiratory causes of infant mortality: progress and challenges.

A marked reduction in infant mortality due to respiratory distress syndrome (RDS) has been reported in previous studies; however, deaths due to RDS are still more common in black infants than white infants. Because advances in respiratory care may have impacted non-RDS respiratory causes of infant mortality as well, the objective of this study was to determine if specific and total non-RDS respiratory causes of infant mortality have changed over time, and if health disparities exist. We analyzed and compared infant deaths due to RDS and other respiratory diseases from 1980 to 2005 in the United States and evaluated outcomes by race and gender. Infant mortality due to non-RDS causes declined more than twofold over this time frame, but not as dramatically as the fivefold decline in RDS deaths. Black compared with white infants had twice the mortality rate due to non-RDS respiratory causes. The most common non-RDS respiratory cause of infant mortality was due to congenital malformations of the respiratory tract, which did not change dramatically over the 25 years studied.

Sleep architecture and behavioral abnormalities in children and adolescents.

OBJECTIVE: To investigate the association between sleep disordered breathing (SDB) and parent report of attention and behavioral problems in children, as well as the association between sleep stage duration and measures of child functioning in a clinically referred sample. METHODS: A chart review was conducted of 95 children with clinical history of SDB who completed an overnight polysomnography study in a pediatric sleep laboratory. Child functioning was assessed at the time of the sleep study by parent report on the Child Behavior Checklist (CBCL). The apnea hypopnea index was used as a measure of SDB severity. RESULTS: The apnea hypopnea index was associated with externalizing behavior, but not attention problems on the CBCL. In children 2-3 years old, stage 4 sleep duration was associated with externalizing behavior. In children 4-16 years old, REM sleep duration was associated with externalizing behavior. CONCLUSIONS: Children with increased SDB severity may be at greater risk for behavioral problems. Differences between the association of sleep stages and externalizing behavior in toddlers compared with older children suggests possible developmental differences in the association between sleep and behavior.

NHLBI training workshop report: the vanishing pediatric pulmonary investigator and recommendations for recovery.

The adequacy of the pipeline of advanced pulmonary fellows to supply appropriately trained and committed researchers to enter academic careers was the major topic of a recently held National Heart Lung and Blood Institute NHLBI Workshop: Respiratory Medicine-Related Research Training for Adult and Pediatric Fellows. The special challenges and opportunities for the academic pediatric pulmonary trainee were discussed as part of this workshop and are presented as a companion article to the report by the full workshop. Surveys were conducted of pediatric chairs of academic departments and pediatric pulmonary training directors in the United States to examine the current status and opportunities for the pediatric pulmonary trainee. Strategies for recruitment and retention of talented young trainees and junior faculty are proposed.

NHLBI workshop: respiratory medicine-related research training for adult and pediatric fellows.

The pulmonary physician-scientist has a special niche to generate basic research findings and apply them to a clinical disease and perhaps impact its medical care. The availability of new high throughput-based scientific technologies in the "omics era" has made this an opportune time for physician scientists to prepare and embark on an academic career in respiratory disease research. However, maintaining an adequate flow through the research pipeline of physician-scientist investigators studying respiratory system diseases is currently a challenge. There may not be a sufficient workforce emerging to capitalize on current research opportunities. The National Heart, Lung, and Blood Institute (NHLBI) organized a workshop to assess ways to attract and properly train advanced fellows to pursue research careers in adult and pediatric lung diseases. Participants included representatives from the various pulmonary training programs, respiratory-related professional societies, and NHLBI staff. Deliberation centered on present barriers that might affect interest in pursuing research training, devising better incentives to attract more trainees, and how current research support offered by the NHLBI and the Professional Societies (in partnership with Industry and Patient Support groups) might be better coordinated and optimized to ensure a continued pipeline of pulmonary investigators. Major recommendations offered are: (1) Attract trainees to pulmonary/critical care medicine-based research careers by increasing research exposure and opportunities for high school, college, and medical students. (2) Increase awareness of the outstanding physician-scientist role models in the lung community for trainees. (3) Facilitate mechanisms by which the lung community (NHLBI, professional societies, and partners) can better support and bridge senior fellows as they transition from Institutional Training Grants (T32) to Career Series (K) awards in their early faculty career development.

Elevated ambient air zinc increases pediatric asthma morbidity.

BACKGROUND: Recent studies indicate that the composition of fine particulate matter [PM

Transition to managed care impacts health care service utilization by children insured by Medicaid.

Purpose. To evaluate the impact of transition to managed care from fee for service on asthma service utilization among Maryland Medicaid insured children. Methods. Healthcare claims from 1997-2000 for children with asthma insured by Maryland Medicaid were extracted and analyzed. Results. Between 1997-2000, inhaled corticosteroid use increased as a proportion of all asthma medications. Outpatient asthma visits increased from 4.2% to 5.9% of all outpatient claims as both asthma-related hospitalizations and emergency department visits decreased. Conclusions. Restructuring of Maryland Medicaid for children from fee for service to managed care was associated with improvement in asthma-related healthcare utilization claims.